Dr. Monaghan's Lab

Welcome to Dr. Daniel Monaghan's laboratory

Research Goals
Funding
Techniques used in the laboratory
Personnel
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Dr. Monaghan's Biographical Information


Research Goals

  • Development of subtype-selective glutamate receptor antagonists to determine the roles of individual receptors in brain function and brain disorders
  • Determine the intracellular signaling pathways by which NMDA receptors regulate neuronal cell function

Funding

Cleft Binding NMDA Receptor Subtype Antagonists

PI: D. Monaghan

Source: NIH/NIMH 5 R01 MH060252-06

The grant Cleft Binding NMDA Receptor Subtype Antagonists supports the development of novel NMDA receptor antagonists that are designed to block the function of distinct subtypes of NMDA receptors. The projects uses a combination of medicinal chemistry, molecular modeling, molecular biology, and electrophysiology to design, make and test new compounds that may be of use in treating Alzheimer's, Huntington's, Parkinsons disease as well as stroke, schizophrenia, and neuropathic pain.  

Evaluation of Potential NR2A-Selective NMDA Receptor Antagonists

PI: D. Monaghan

Source: Lilly Research Laboratories

We will be evaluating the NMDA receptor subtype-selectivity of various compounds made by Lilly. We will express recombinant rat NMDA receptor subunits into frog oocytes. After receptor protein is expressed, we activate NMDA receptors by bath applying L-glutamate and glycine. Using two-electrode voltage clamp, we can study the potency of the Lilly compounds at blocking dist9inct NMDA receptor subtypes - NR1/NR2A, NR1/NR2B, and perhaps at NR1/NR2C and NR1/NR2D NMDA receptors. The chemistry of the compounds evaluated does not overlap with the chemicals that we are studying in our NIH grant. Hence, the work should serve as a complement to our NIH studies. 

Development of Novel, subtype-Selective NMDA Receptor Agents

PI: D. Monaghan

Source: UNeMED

The project is to characterize a set of compounds as novel NMDA receptor antagonists that are subtype selective. Subtype-selective NMDA receptor antagonists have several potential therapeutic applications. However, to date, most NMDA receptor subtypes do not have selective antagonists available. The experiments use recombinant NMDA receptors expressed in Xenopus oocytes and determine the potency of compounds to inhibit glutamate-evoked responses at NMDA receptors. The compounds to be evaluated in this study do not overlap with those being studied in parallel NIH-funded studies.


Techniques used in the laboratory
Molecular biology (construction of cDNA point mutations and chimeras, PCR, cRNA synthesis, yeast two-hybrid)

Neuroanatomy and neuropharmacology (quantitative receptor autoradiography, in situ hybridization, immunohistochemistry, radioligand binding)

Protein chemistry (immunoprecipitation, Western blotting, protein phosphorylation, two dimensional peptide mapping)

Electrophysiology (two electrode voltage clamp of frog oocytes; hippocampal extracellular recordings, patch-clamp of brain cells in hippocampal slices, dynamic calcium imaging)

Cell culture (primary cells and brain tissue slice cultures)

Molecular modeling (homology receptor modeling and drug-receptor docking)


Personnel

Kiran_Sapkota_2012

Kiran Sapkota
Graduate Student
kiran.sapkota@unmc.edu 

   

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Dr. Monaghan's Biographical Information

 

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